What is it about?
When cancer spreads to other parts of the body, some cancer cells can “fall asleep” and stay hidden for months or even years after the main tumor has been removed. These sleeping cells are thought to be the reason why cancer sometimes comes back long after treatment. In this study, we found that dormant breast cancer cells that travel to the lungs enter a quiet, inactive state. They do not wake up on their own. Instead, inflammation in the lungs — such as that caused by the chemotherapy drug bleomycin — can jolt them awake. This gave us a useful way to study how hidden cancer cells restart their growth. Once awakened, the cells change their character: they shift into a state where they can grow again and form new tumors. Importantly, they can remain in this “awakened” state without needing continued inflammatory signals from the surrounding lung tissue. We discovered that certain signals released by immune cells, especially a type called M2 macrophages, play a key role in pushing dormant cancer cells into this growth-ready state. By understanding exactly how sleeping cancer cells wake up, we may be able to design future treatments that keep them dormant — and prevent cancer from coming back.
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Photo by National Institute of Allergy and Infectious Diseases on Unsplash
Why is it important?
When breast cancer spreads to other parts of the body, it is usually what makes the disease fatal. The real danger comes from the fact that these new tumors, called metastases, can show up long after the first tumor has been treated — sometimes years or even decades later. This happens because some cancer cells escape from the original tumor and hide silently in distant organs. While “asleep,” they cannot be detected by current scans and are unaffected by today’s treatments. Then, suddenly, some of them “wake up,” start multiplying, and grow into new, often life-threatening tumors. Scientists are working urgently to understand how these hidden cells go to sleep and, more importantly, what causes them to wake up. Solving this puzzle could be the key to stopping breast cancer from coming back.
Perspectives
The importance of this study comes from three main points. First, it shows that sleeping cancer cells do not wake up on their own. Instead, changes in their surroundings, or the “neighborhood” of tissue they live in, trigger them to start growing again. Second, this research introduces a reliable new model that scientists can use to study how dormant cancer cells become active. Third, the findings offer new ideas for preventing cancer from coming back in patients. Looking ahead, other researchers will need to test whether the same process of waking up happens in different types of cancer.
Jingwei Zhang
Whitehead Institute for Biomedical Research
Read the Original
This page is a summary of: Inflammation awakens dormant cancer cells by modulating the epithelial–mesenchymal phenotypic state, Proceedings of the National Academy of Sciences, September 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2515009122.
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